The blood-brain barrier maintains a homeostatic environment in the central nervous system (CNS). The capillaries that supply the blood to the brain have tight junctions which block passage of most molecules through the capillary endothelial membranes. While the membranes do allow passage of lipid soluble materials, water soluble materials such as glucose, proteins and amino acids do not pass through the blood brain barrier. Mediated transport mechanisms exist to transport glucose and essential amino acids across the blood brain barrier. Active transport mechanisms remove molecules which become in excess, such as potassium, from the brain. However, the blood brain barrier impedes the delivery of drugs to the CNS.
Many neurological diseases result from cellular defects in the CNS. In particular, many lysosomal storage diseases affect cells of the CNS and result in mild to serious neurological symptoms. Accordingly, the ability to deliver therapeutic compositions to the CNS is an important aspect of an effective treatment for many diseases, including many lysosomal storage diseases.
Methods have been designed to deliver needed drugs to the CNS such as direct delivery within the CNS by intrathecal delivery. However, methods are not available in the art to efficiently deliver drugs, and particularly protein-based drugs, from the blood stream to the CNS through the blood brain barrier.
Therefore, there is a need in the art for methods to deliver proteins to the brain parenchyma on the CNS side of the blood brain barrier, and in particular to deliver proteins to the lysosomes of cells in the CNS.